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. 2004 Jul 13;74(1):1–7. doi: 10.1002/jmv.20138

Persistent infection of SARS coronavirus in colonic cells in vitro

Paul KS Chan 1,2,✉, Ka‐Fai To 3, Anthony WI Lo 3, Jo LK Cheung 2, Ida Chu 2, Florence WL Au 3, Joanna HM Tong 3, John S Tam 1,2, Joseph JY Sung 1, Ho‐Keung Ng 3
PMCID: PMC7166317  PMID: 15258961

Abstract

Severe acute respiratory syndrome coronavirus (SARS‐CoV) can produce gastrointestinal symptoms. The intestinal tract is the only extrapulmonary site where viable viruses have been detected. This study examined seven established human intestinal cell lines, DLD‐1, HCT‐116, HT‐29, LoVo, LS‐180, SW‐480 and SW‐620, for their permissiveness to SARS‐CoV infection. The results showed that only LoVo cells were permissive to SARS‐CoV infection as evident by positive findings from indirect immunofluorescence staining for intracellular viral antigens, in situ hybridization for intracellular viral RNA, and electron microscopy for intracellular viral particles. In contrast to Vero cells, SARS‐CoV did not produce cytopathic effects on LoVo cells. However, LoVo cells were found to be highly permissive for productive infection with a high viral titre (>3 × 107 viral copies/ml) produced in culture supernatant following a few days of incubation. SARS‐CoV established a stable persistent chronic infection that could be maintained after multiple passages. Being a cell line of human origin, LoVo cells could be a useful in vitro model for studying the biology and persistent infection of SARS‐CoV. Our results on the expression of angiotensin‐converting enzyme 2 (ACE2), a recently identified cellular receptor for SARS‐CoV, in these cell lines indicated that it might not be the sole determinant for cells to be susceptible to SARS‐CoV infection. J. Med. Virol. 74:1–7, 2004. © 2004 Wiley‐Liss, Inc.

Keywords: SARS, coronavirus, persistent infection, in vitro, receptor, ACE2

REFERENCES

  1. Chan PKS, Tam JS, Lam CW, Chan E, Wu A, Li CK, Buckley TA, Ng KC, Joynt GM, Cheng FWT, To KF, Lee N, Hui DS, Cheung JL, Chu I, Liu E, Chung SS, Sung JJY. 2003. Human metapneumovirus detection in patients with severe acute respiratory syndrome. Emerg Infect Dis 9: 1058–1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chan PKS, Ng KC, Chan RCW, Lam RKY, Chow VCY, Hui M, Wu A, Lee N, Yap HY, Cheng FWT, Sung JJY, Tam JS. 2004a. Immunofluorescence assay for serologic diagnosis of SARS. Emerg Infect Dis 10: 530–532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chan PKS, To WK, Ng KC, Lam RKY, Ng TK, Chan RCW, Wu A, Yu WC, Lee N, Hui DSC, Lai ST, Hon EKL, Li CK, Sung JJY, Tam JS. 2004b. Laboratory Diagnosis of SARS. Emerg Infect Dis 10: 825–831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drosten C, Gunther S, Preiser W, van der WS, Brodt HR, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier RA, Berger A, Burguiere AM, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra JC, Muller S, Rickerts V, Sturmer M, Vieth S, Klenk HD, Osterhaus AD, Schmitz H, Doerr HW. 2003. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348: 1967–1976. [DOI] [PubMed] [Google Scholar]
  5. Fouchier RA, Kuiken T, Schutten M, van Amerongen G, van Doornum GJ, van den Hoogen BG, Peiris M, Lim W, Stohr K, Osterhaus AD. 2003. Aetiology: Koch's postulates fulfilled for SARS virus. Nature 423: 240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harmer D, Gilbert M, Borman R, Clark KL. 2002. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 532: 107–110. [DOI] [PubMed] [Google Scholar]
  7. Hon KLE, Leung CW, Cheng WT, Chan PKS, Chu WCW, Kwan YW, Li AM, Fong NC, Ng PC, Chiu MC, Li CK, Tam JS, Fok TF. 2003. Clinical presentations and outcome of severe acute respiratory syndrome in children. Lancet 361: 1701–1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348: 1953–1966. [DOI] [PubMed] [Google Scholar]
  9. Kuiken T, Fouchier RAM, Schutten M, Rimmelzwaan GF, van Amerongen G, van Riel D, Laman JD, de Jong T, van Doornum G, Lim W, Ling AE, Chan PKS, Tam JS, Zambon MC, Gopal R, Drosten C, van der WS, Escriou N, Manuguerra JC, Stohr K, Peiris JSM, Osterhaus ADME. 2003. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet 362: 263–270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, Ahuja A, Yung MY, Leung CB, To KF, Lui SF, Szeto CC, Chung S, Sung JJY. 2003. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348: 1986–1994. [DOI] [PubMed] [Google Scholar]
  11. Leung WK, To KF, Chan PKS, Chan HL, Wu AK, Lee N, Yuen KY, Sung JJY. 2003. Enteric involvement of severe acute respiratory syndrome‐associated coronavirus infection. Gastroenterology 125: 1011–1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. 2003. Angiotensin‐converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426: 450–454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Marra MA, Jones SJ, Astell CR, Holt RA, Brooks‐Wilson A, Butterfield YS, Khattra J, Asano JK, Barber SA, Chan SY, Cloutier A, Coughlin SM, Freeman D, Girn N, Griffith OL, Leach SR, Mayo M, McDonald H, Montgomery SB, Pandoh PK, Petrescu AS, Robertson AG, Schein JE, Siddiqui A, Smailus DE, Stott JM, Yang GS, Plummer F, Andonov A, Artsob H, Bastien N, Bernard K, Booth TF, Bowness D, Czub M, Drebot M, Fernando L, Flick R, Garbutt M, Gray M, Grolla A, Jones S, Feldmann H, Meyers A, Kabani A, Li Y, Normand S, Stroher U, Tipples GA, Tyler S, Vogrig R, Ward D, Watson B, Brunham RC, Krajden M, Petric M, Skowronski DM, Upton C, Roper RL. 2003. The Genome sequence of the SARS‐associated coronavirus. Science 300: 1399–1404. [DOI] [PubMed] [Google Scholar]
  14. Ng ML, Tan SH, See EE, Ooi EE, Ling AE. 2003a. Proliferative growth of SARS coronavirus in Vero E6 cells. J Gen Virol 84: 3291–3303. [DOI] [PubMed] [Google Scholar]
  15. Ng ML, Tan SH, See EE, Ooi EE, Ling AE. 2003b. Early events of SARS coronavirus infection in vero cells. J Med Virol 71: 323–331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK, Yuen KY. 2003a. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361: 1319–1325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, Law KI, Tang BS, Hon TY, Chan CS, Chan KH, Ng JS, Zheng BJ, Ng WL, Lai RW, Guan Y, Yuen KY. 2003b. Clinical progression and viral load in a community outbreak of coronavirus‐associated SARS pneumonia: A prospective study. Lancet 361: 1767–1772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Poutanen SM, Low DE, Henry B, Finkelstein S, Rose D, Green K, Tellier R, Draker R, Adachi D, Ayers M, Chan AK, Skowronski DM, Salit I, Simor AE, Slutsky AS, Doyle PW, Krajden M, Petric M, Brunham RC, McGeer AJ. 2003. Identification of severe acute respiratory syndrome in Canada. N Engl J Med 348: 1995–2005. [DOI] [PubMed] [Google Scholar]
  19. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, DeRisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C, Ksiazek TG, Rollin PE, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen‐Rasmussen M, Fouchier R, Gunther S, Osterhaus AD, Drosten C, Pallansch MA, Anderson LJ, Bellini WJ. 2003. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300: 1394–1399. [DOI] [PubMed] [Google Scholar]
  20. To KF, Tong JHM, Chan PKS, Au FWL, Chim SSC, Chan AKC, Cheung JLK, Liu EYM, Tse GMK, Lo AWI, Lo DYM, Ng HK. 2004. Tissue and cellular tropisms of the coronavirus associated with Severe Acute Respiratory Syndrome—An in‐situ hybridization study of fatal cases. J Pathol 202: 157–163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tse GMK, To KF, Chan PKS, Lo AWI, Ng KC, Wu A, Lee N, Wong HC, Mak SM, Chan KF, Hui DSC, Sung JJY, Ng HK. 2004. Pulmonary pathological features in coronavirus associated severe respiratory syndrome (SARS). J Clin Pathol 57: 260–265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wong SK, Li W, Moore MJ, Choe H, Farzan M. 2004. A 193‐amino‐acid fragment of the SARS coronavirus S protein efficiently binds angiotensin‐converting enzyme 2. J Biol Chem 279: 3197–3201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. World Health Organization . 2003. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003 (revised 25 September 2003) http://www.who.int/csr/sars/country/table2003_09_23/en/print.html (assessed on 30 December 2003).

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